The characterization of idiotypic determinants and the generation of anti-idiotypic reagents have provided powerful tools with which to analyze a given immune response. The idiotype network developed during the course of an immune response provides conceptual insight into the host response to a given antigen. It is proposed to analyze the idiotype network initiated by a host in response to a hepatitis B virus infection or immunization with hepatitis B surface antigen (HBsAg). The idiotypes that are expressed on human and mouse antibodies to HBsAG (anti-HBs) will be characterized. The expression of these idiotypic determinants on anti-HBs produced in naturally infected and in immunized individuals will be analyzed. The identification of a major common idiotype on human anti-HBs sera will be used in detecting variable region antibody gene differences among individuals. The genetics of the immune response in different strains of mice will be characterized using the reagents prepared against both human anti-HBs idiotypes and mouse monoclonal anti-HBs idiotypes. The epitopes associated with HBsAg and with synthetic HBsAg peptides will be identified. In addition, we will further examine the use of anti-idiotype antibodies to modulate the immune response to HBsAg in experimental animals. The results of these experiments will give insight into whether idiotype networks, expression of particular idiotypes, or both are important in the host response to hepatitis B virus.